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高葡萄糖浓度促进糖尿病小鼠体内耐万古霉素金黄色葡萄球菌的万古霉素增强生物膜形成

High Glucose Concentration Promotes Vancomycin-Enhanced Biofilm Formation of Vancomycin-Non-Susceptible Staphylococcus aureus in Diabetic Mice.

作者信息

Hsu Chi-Yu, Shu Jwu-Ching, Lin Mei-Hui, Chong Kowit-Yu, Chen Chien-Cheng, Wen Shu-Min, Hsieh Yi-Ting, Liao Wan-Ting

机构信息

Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, No. 259, Wenhua 1st Road, Guishan, Taoyuan 333, Taiwan.

Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, No. 259, Wenhua 1st Road, Guishan, Taoyuan 333, Taiwan; Research Center for Pathogenic Bacteria, Chang Gung University, No. 259, Wenhua 1st Road, Guishan, Taoyuan 333, Taiwan; Department of Laboratory Medicine, Chang Gung Memorial Hospital, No. 5, Fusing St., Guishan, Taoyuan 333, Taiwan.

出版信息

PLoS One. 2015 Aug 5;10(8):e0134852. doi: 10.1371/journal.pone.0134852. eCollection 2015.

Abstract

We previously demonstrated that vancomycin treatment increased acquisition of eDNA and enhanced biofilm formation of drug-resistant Staphylococcus aureus through a cidA-mediated autolysis mechanism. Recently we found that such enhancement became more significant under a higher glucose concentration in vitro. We propose that besides improper antibiotic treatment, increased glucose concentration environment in diabetic animals may further enhance biofilm formation of drug-resistant S. aureus. To address this question, the diabetic mouse model infected by vancomycin-resistant S. aureus (VRSA) was used under vancomycin treatment. The capacity to form biofilms was evaluated through a catheter-associated biofilm assay. A 10- and 1000-fold increase in biofilm-bound bacterial colony forming units was observed in samples from diabetic mice without and with vancomycin treatment, respectively, compared to healthy mice. By contrast, in the absence of glucose vancomycin reduced propensity to form biofilms in vitro through the increased production of proteases and DNases from VRSA. Our study highlights the potentially important role of increased glucose concentration in enhancing biofilm formation in vancomycin-treated diabetic mice infected by drug-resistant S. aureus.

摘要

我们之前证明,万古霉素治疗通过cidA介导的自溶机制增加了胞外DNA的获取,并增强了耐药金黄色葡萄球菌的生物膜形成。最近我们发现,在体外较高葡萄糖浓度下,这种增强作用变得更加显著。我们提出,除了不恰当的抗生素治疗外,糖尿病动物体内葡萄糖浓度升高的环境可能会进一步增强耐药金黄色葡萄球菌的生物膜形成。为了解决这个问题,我们在万古霉素治疗下使用了耐万古霉素金黄色葡萄球菌(VRSA)感染的糖尿病小鼠模型。通过导管相关生物膜试验评估生物膜形成能力。与健康小鼠相比,在未接受和接受万古霉素治疗的糖尿病小鼠样本中,观察到生物膜结合细菌集落形成单位分别增加了10倍和1000倍。相比之下,在没有葡萄糖的情况下,万古霉素通过增加VRSA蛋白酶和DNase的产生,降低了体外生物膜形成的倾向。我们的研究强调了葡萄糖浓度升高在增强万古霉素治疗的、感染耐药金黄色葡萄球菌的糖尿病小鼠生物膜形成中可能发挥的重要作用。

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